Process for the preparation of 5-acylpyrimidines

ABSTRACT

A process for the preparation of a 5-acylpyrimidine of the formula ##STR1## in which R is an organic radical comprising reacting a methyl ketone of the formula 
     
         R--CO--Ch.sub.3 
    
      in a first stage with a formylating reagent in the presence of a base to form an enolketone of the formula 
     
         R--CO--CH═CH--OR.sup.10 
    
     in which 
     R 10  represents hydrogen or a base radical, thereafter reacting the enolketone in 2nd and 3rd stages with formamidine or a formamidine salt, and with an amino-formylating agent, and, in a 4th stage heating to cyclize the compound formed. 
     The end products, some of which are new, are intermediates for making herbicides.

This is a division of application Ser. No. 769,639, filed Aug. 26, 1985,now U.S. Pat. No. 4,713,456.

The present invention relates to a new process for the preparation of5-acylpyrimidines, some of which are known and which can be used asintermediates for the preparation of substances having a plantgrowth-regulating and fungicidal activity.

It is already known that pyrimidinylcarbinols can be used asintermediates for the preparation of benzyl pyrimidinyl-alkyl etherswith plant growth-regulating and fungicidal properties (See U.S. Pat.No. 4,436,907 issued Mar. 13, 1984).

Thus, benzyl pyrimidinyl-alkyl ethers are obtained whenpyrimidinylcarbinols are reacted with benzyl halides in accordance withthe following equation: ##STR2## R¹ =optionally substituted phenyl, R²=alkyl, optionally substituted cycloakyl or optionally substitutedphenyl and

Hal=halogen.

The disadvantage of this known process is, however, that thepyrimidinylcarbinols required as starting substances are producible onlywith difficulty. Thus, these pyrimidinylcarbinols can be prepared byreacting pyrimidinyl halides with an alkali metal-organic compound, suchas, for example, n-butyl-lithium, and then with corresponding aldehydesat low temperatures, for example between -100° and -120° C. (See U.S.Pat. No. 4,436,907 issued Mar. 13, 1984.) The use of organometalliccompounds at such low temperatures makes practical application of thisprocess on an industrial scale virtually impossible.

Another disadvantage of this process is that the price of thepyrimidinyl halide required as a starting substance is extremely high.There is therefore a great interest in a process which allows a moresimpler synthesis of the highly active benzyl pyrimidinyl-alkyl ethersof the abovementioned general formula.

It is also known that 5-acetylpyrimidine can be obtained from5-acetyl-uracil via 2,4-dichloro-5-acetylpyrimidine by reductivedehalogenation (compare Arch. Pharm. 299,362 (1966)). The yield of endproduct in this multi-stage process is, however, very low.

It is furthermore known that 5-(2-hydroxybenzoyl)pyrimidine is obtainedwhen chromone-3-carbaldehyde is reacted with formamidine (compareSynthesis 1976, 274). The yield here is also unsatisfactory. Inaddition, this process variant cannot be generalized for5-benzoylpyrimidines with any desired substituents in the phenyl part.

It is moreover known that certain substituted 5-acylpyrimidines can beobtained if a methyl ketone is formylated, the product is furtherreacted to give the enol-acetate, the enol-acetate is formylated withethyl orthoformate and, finally, cyclization to the pyrimidine iscarried out with, for example, methylisothiourea (compare Acta Chemica.Scandinavia B 36, 529-31 (1982)). This process has the disadvantage of amulti-stage reaction, in which the intermediates are isolated.

It has now been found that 5-acylpyrimidines of the formula ##STR3## inwhich R represents alkyl, alkenyl, alkinyl, optionally substitutedcycloalkyl, optionally substituted cycloalkylalkyl, optionallysubstituted phenyl, optionally substituted heteroaryl or the groupings##STR4## wherein R³ represents halogen;

R⁴ represents hydrogen or halogen;

R⁵ represents alkenyl, alkinyl or the CHO group and derivatives thereof;

R⁶ represents cyano, optionally substituted phenyl or the groupings--XR⁷ and --CONR⁸ R⁹,

wherein

R⁷ represents alkyl, halogenoalkyl, optionally substituted phenyl oroptionally substituted phenylalkyl;

R⁸ represents hydrogen, alkyl or optionally substituted phenyl;

R⁹ represents hydrogen or alkyl;

X represents oxygen or sulphur and

the index n represents the number 0, 1 or 2, can be prepared by aprocess in which methyl ketones of the formula

    R--CO--CH.sub.3                                            (II)

in which

R has the above mentioned meaning,

(a) are reacted in a 1st stage with a formylating reagent in thepresence of a base and if appropriate in the presence of a diluent and,if appropriate, the product is acidified, and thereafter, in a 2ndstage, the enolketones formed, of the formula

    R--CO--CH═CH--OR.sup.10                                (III)

in which

R has the abovementioned meaning and

R¹⁰ represents hydrogen or a base radical, are reacted, with or withoutintermediate isolation, with formamidine, it being possible for theformamidine optionally to be in the form of a formamidine salt, ifappropriate in the presence of a diluent; and subsequently, in a 3rdstage, the formamidine derivatives formed, of the formula

    R--CO--CH.sub.2 --CH═N--CH═NH                      (IV)

in which

R has the abovementioned meaning, are reacted, with or withoutintermediate isolation, with an amino-formylating agent, if appropriatein the presence of a diluent; and, in a 4th stage, the compounds formed,of the formula ##STR5## in which R has the abovementioned meaning and

Y represents the nitrogen-containing radical of an amino-formylatingagent,

are cyclized by means of heat, with or without intermediate isolation;or

(b) are reacted, in a 1st stage with a formylating reagent in thepresence of a base and, if appropriate, in the presence of a diluent,and the product is then acidified, and thereafter, in a 2nd stage, theenol-ketones formed, of the formula

    R--CO--CH═CH--OH                                       (IIIa)

in which

R has the abovementioned meaning, are reacted, with or withoutintermediate isolation, with an amino-formylating agent, if appropriatein the presence of a diluent, and, in a 3rd stage, the compounds formed,of the formula ##STR6## in which R and Y have the abovementionedmeaning, are reacted, with or without intermediate isolation, withformamidine, if appropriate in the presence of a diluent, and theproduct is then cyclized by means of heat.

Finally, it has been found that the 5-acylpyrimidines of the formula (I)are particularly suitable as intermediates for the preparation of benzylpyrimidinyl-alkyl ethers with a plant growth-regulating and fungicidalactivity.

The course of the process according to the invention is to be describedas extremely surprising both in variant (a) and in variant (b).

Thus, in view of the known prior art, it was to be expected that theintermediate of the formula (IV) formed when carrying out variant (a)(preparation from the formal diketone R--CO--CH₂ --CHO and formamidine)cyclizes to give the corresponding 4-substituted pyrimidine inaccordance with the following equation: ##STR7##

Such cyclizations of β-diketones with amidines to give 4-substitutedpyrimidines have frequently been described in the literature (compare,for example, D. J. Brown, The Pyrimidines, page 36, IntersciencePublishers, 1962). Surprisingly, however, such a cyclization reactiondoes not occur in the course of variant (a) of the process according tothe invention.

It is also surprising that when carrying out process variant (b), thereaction of the enol-ketone of the formula (IIIa) with a basicamino-formylating agent (compare 2nd stage) to give compounds of theformula (VI) is effected without the acid OH group of the enol-ketone ofthe formula (IIIa) being alkylated. In fact, it is known from the priorart that acid OH groups can be alkylated with amino-formylating agents(compare Synthesis 1983, 135-136).

Finally, it is also surprising that the intermediate of the formula (VI)can further react as such in the course of the reaction according toprocess variant (b) without decarbonylation occurring to the expecteddegree in accordance with the following equation: ##STR8##

The exceptionally easy decarbonylation of compounds of the type offormula (VI) is known from the literature (compare Collect. Czech. Comm.28, 869 et seq.). An analogous reaction in the course of variant (b) ofthe process according to the invention was therefore to be expected.

The process according to the invention is distinguished by a number ofadvantages. Thus, the desired 5-acylpyrimidines of the formula (I) canbe prepared in a simple manner--even on an industrial scale. The yieldsare relatively high. It is particularly advantageous that none of theintermediates which arise have to be isolated, so that the process is inprinciple a one-pot process, which means that particularly goodspace/time yields can be achieved. Moreover, it should be emphasizedthat the 5-acylpyrimidines of the formula (I) which are accessible byprocess variants (a) and (b) according to the invention, which differonly in the sequence of the addition of the formylating andamino-formylating agents, can be converted into benzyl pyrimidinyl-alkylethers, which have plant growth-regulating and fungicidal properties, bysubsequent reduction and reaction of the carbinols thereby formed withbenzyl halides. A method for the synthesis of the plantgrowth-regulating and fungicidal active compounds which is substantiallysimpler than the processes known hitherto is therefore now available. Inaddition, in contrast to the previous process, this new process can alsobe applied on an industrial scale without difficulties.

Only some of the 5-acylpyrimidines which can be prepared by the processaccording to the invention were known hitherto. The 5-acylpyrimidines ofthe formula ##STR9## in which R¹¹ represents straight-chain alkyl withmore than 4 carbon atoms, branched alkyl, alkenyl, alkinyl, optionallysubstituted cycloalkyl, optionally substituted cycloalkylalkyl,optionally substituted phenyl (with the exception of 2-hydroxyphenyl),optionally substituted heteroaryl and the groupings ##STR10## wherein R³represents halogen;

R⁴ represents hydrogen or halogen,

R⁵ represents alkenyl, alkinyl or the CHO group and derivatives thereof;

R⁶ represents cyano, optionally substituted phenyl or the groupings--XR⁷ and --CONR⁸ R⁹,

wherein

R⁷ represents alkyl, halogenoalkyl, optionally substituted phenyl oroptionally substituted phenylalkyl;

R⁸ represents hydrogen, alkyl or optionally substituted phenyl;

R⁹ represents hydrogen or alkyl;

X represents oxygen or sulphur and

the index n represents the number 0, 1 or 2, are new.

In the compounds of the formula (Ia) R¹¹ preferably representsstraight-chain or branched alkyl with 5 to 12 carbon atoms,straight-chain or branched alkenyl with 3 to 6 carbon atoms,straight-chain or branched alkinyl with 3 to 6 carbon atoms orcycloalkyl or cycloalkylalkyl with in each case 3 to 7 carbon atoms inthe cycloalkyl part and 1 to 4 carbon atoms in the alkyl part and ineach case optionally mono-, di- or tri-substituted by identical ordifferent alkyl substituents with 1 to 4 carbon atoms; or representsphenyl which is optionally mono-, di- or tri-substuted by identical ordifferent substituents, substituents which may be mentioned being:halogen, alkyl, alkoxy and alkylthio with in each case 1 to 4 carbonatoms; halogenoalkyl, halogenoalkoxy and halogenoalkylthio with in eachcase 1 to 4 carbon atoms and 1 to 5 identical or different halogenatoms, such as fluorine and chlorine atoms; nitro, cyano andalkoxycarbonyl with 1 to 4 carbon atoms in the alkoxy part; and phenyland phenoxy, in each case optionally substituted by halogen; orfurthermore represents 5- to 6-membered heteroaryl which has 1 to 3hetero-atoms, such as oxygen, nitrogen and/or sulphur, and is optionallymono-, di- or tri- substituted by identical of different substituents,possible substituents being the abovementioned substituents on phenyl,or represents the groupings ##STR11## wherein R³ preferably representsfluorine, chlorine or bromine;

R⁴ preferably represents hydrogen, fluorine, chlorine or bromine;

R⁵ preferably represents straight-chain or branched alkenyl with 2 to 4carbon atoms, straight-chain or branched alkinyl with 3 to 5 carbonatoms, or the CHO group and derivatives thereof, such as oximes, oximeethers and acetals, for example alkoximinomethyl with 1 to 4 carbonatoms in each alkoxy part, dialkoxymethyl with 1 to 4 carbon atoms ineach alkoxy part and optionally substituted dixolanes and dioxanes;

R⁶ preferably represents cyano, or represents phenyl which is optionallymono-, di- or tri-substituted by identical or different substituents,possible substituents being the substituents on phenyl which havealready been mentioned above, or represents the groupings --XR⁷ and--CONR⁸ R⁹,

wherein

R⁷ preferably represents straight-chain or branched alkyl with 1 to 6carbon atoms or halogenoalkyl with 1 to 4 carbon atoms and 1 to 5identical or different halogen atoms, such as fluorine and chlorineatoms, or represents phenyl or phenylalkyl, with 1 or 2 carbon atoms inthe alkyl part, each of which is optionally mono-, di- ortri-substituted by identical or different substituents, possiblesubstituents in each case being the substituents on phenyl which havealready been mentioned above;

R⁸ preferably represents hydrogen or straight-chain or branched alkylwith 1 to 4 carbon atoms, or represents phenyl which is optionallymono-, di- or tri-substituted by identical or different substituents,possible substituents being the substituents on phenyl which havealready been mentioned above;

R⁹ preferably represents hydrogen or straight-chain or branched alkylwith 1 to 4 carbon atoms;

X represents oxygen or sulphur and

n represents the number 0, 1 or 2.

Particularly preferred compounds of the formula (Ia) are those

in which

R¹¹ represents straight-chain alkyl with 5 to 8 carbon atoms, orrepresents isopropyl, tert.-butyl, neopentyl, allyl or lpropargyl, orrepresents cyclopropyl, cyclobutyl, cyclpentyl or cyclohexyl, each ofwhich is optionally mono- or di-substituted by identical or differentsubstituents from the group comprising methyl, ethyl, isopropyl andtert.-butyl, or represents phenyl which is optionally mono- ordi-substituted by identical or different substituents, substituentswhich may be mentioned being: fluorine, chlorine, methyl, ethyl,isopropyl, tert.-butyl, methoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, nitro, cyano and methoxycarbonyl,and phenyl and phenoxy, each of which is optionally substituted bychlorine or fluorine; or furthermore represents furyl, thienyl,benzofuryl, benzothienyl, pyridinyl or pyrimidinyl, each of which isoptionally mono- or disubstituted by identical or differentsubstituents, possible substituents being the above-mentionedsubstituents on phenyl; or represents the groupings ##STR12## wherein R³represents fluorine or chlorine;

R⁴ represents hydrogen, fluorine or chlorine;

R⁵ represents vinyl, propargyl, the --CH═O group, methoximinomethyl,dimethoxymethyl or the dioxolane or 1,3-dioxane radical;

R⁶ represents cyano or phenyl which is optionally mono- ordi-substituted by identical or different substituents, possiblesubstituents being the substituents on phenyl which have already beenmentioned above, or represents the groupings --XR⁷ and --CONR⁸ R⁹ ;

wherein

R⁷ represents straight-chain or branched alkyl with 1 or 4 carbon atomsor halogenoalky with 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, such as fluorine and chlorine atoms, orrepresents phenyl or benzyl, each of which is optionally mono- ord-substituted by identical or different substituents, possiblesubstituents in each case being the substituents on phenyl which havealready been mentioned above;

R⁸ represents hydrogen, methyl, ethyl, isopropyl or phenyl which isoptionally mono- or di-substituted by identical or differentsubstituents, possible substituents being the substituents on phenylwhich have already been mentioned above;

R⁹ represents hydrogen, methyl or isopropyl;

X represents oxyen or sulphur and

n represents the number 0, 1 or 2.

If, for example, methoxy-tert.-butyl methyl ketone is used as thestarting substance, ethyl formate in the presence of sodium methylate isused as the formylating reagent, formamidine is used in the form of theacetate and N,N-dimethylformamide dimethyl acetal is used as theamino-formylating agent, the course of the reaction of the processaccording to the invention in variant (a) can be represented by thefollowing equation: ##STR13##

If, for example, 2,4-dichlorophenyl methyl ketone is used as thestarting substance, ethyl formate in the presence of sodium methylate isused as the formylating reagent, N,N-dimethylformamide dimethyl acetalis used as the amino-formylating agent and formamidine is used for thecyclization, the course of the reaction of the process according to theinvention in variant (b) can be represented by the following equation:##STR14##

Formula (II) provides a general definition of the methyl ketonesrequired as starting substances in carrying out the process according tothe invention. In this formula

R preferably represents straight-chain or branched alkyl with 1 to 12carbon atoms, straight-chain or branched alkenyl with 3 to 6 carbonatoms, straight-chain or branched alkinyl with 3 to 6 carbon atoms orcycloalkyl and cycloalkylalkyl with in each case 3 to 7 carbon atoms inthe alkyl part and in each case optionally mono-, di- or tri-substitutedby identical or different alkyl substituents with 1 to 4 carbon atoms;or represents phenyl which is optionally mono-, di- or tri-substitutedby identical or different substituents, substituents which may bementioned being: halogen; alkyl, hydroxyl, alkoxy and alkylthio with ineach case 1 to 4 carbon atoms; halogenoalkyl, halogenoalkoxy andhalogenoalkylthio with in each case 1 to 4 carbon atoms and 1 to 5identical or different halogen atoms, such as fluorine and chlorineatoms; nitro, cyano and alkoxycarbonyl with 1 to 4 carbon atoms in thealkoxy part, and phenyl and phenoxy, in each case optionally substitutedby halogen; or furthermore represents 5- to 6-membered heteroaryl whichhas 1 to 3 hetero-atoms, such as oxygen, nitrogen and/or sulphur, and isoptionally mono-, di- or tri-substituted by identical or differentsubstituents, possible substituents being the abovementionedsubstituents on phenyl, or represents the groupings ##STR15## wherein R³preferably represents fluorine, chlorine or bromine;

R⁴ preferably represents hydrogen, fluorine, chlorine or bromine;

R⁵ preferably represents straight-chain or branched alkenyl with 2 to 4carbon atoms, straight-chain or branched alkinyl with 3 to 5 carbonatoms, or the CHO group and derivatives thereof, such as oximes, oximeethers and acetals, for example alkoximinomethyl with 1 to 4 carbonatoms in each alkoxy part, dialkoxymethyl with 1 to 4 carbon atoms ineach alkoxy part and optionally substituted dioxolanes and dioxanes;

R⁶ preferably represents cyano, or represents phenyl which is optionallymono-, di- or tri-substituted by identical or different substituents,possible substituents being the substituents or phenyl which havealready been mentioned above, or represents the groupings --XR⁷ and--CONR⁸ R⁹,

wherein

R⁷ preferably represents straight-chain or branched alkyl with 1 to 6carbon atoms or halogenoalkyl with 1 to 4 carbon atoms and 1 to 5identical or different halogen atoms, such as fluorine and chlorineatoms, or represents phenyl or phenylalkyl, with 1 or 2 carbon atoms inthe alkyl part, each of which is optionally mono-, di- ortri-substituted by identical or different substituents, possiblesubstituents in each case being the substituents on phenyl which havealready been mentioned above;

R⁸ preferably represents hydrogen or straight-chain or branched alkylwith 1 to 4 carbon atoms, or represents phenyl which is optionallymono-, di- or tri-substituted by identical or different substituents,possible substituents being the substituents on phenyl which havealready been mentioned above;

R⁹ preferably represents hyrogen or straight-chain or branched alkylwith 1 to 4 carbon atoms;

X represents oxygen or sulphur and

n represents the number 0, 1 or 2.

Particularly preferred compounds of the formula (II) are those

in which

R represents methyl, ethyl, n-propyl, isopropyl, n-butyl, tert.-butyll,n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, allyl or propargyl, orrepresents cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, each ofwhich is optionally mono- or di-substituted by identical or differentsubstituents from the group comprising methyl, ethyl, isopropyl andtert.-butyl, or represents phenyl which is optionally mono- ordi-substituted by identical or different substituents, substituentswhich may be mentioned being: fluorine, chlorine, hydroxyl, methyl,ethyl, isopropyl, tert.-butyl, methoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, nitro, cyano and methoxycarbonyl,and phenyl and phenoxy, each of which is optionally substituted byfluorine or chlorine; or furthermore represents furyl, thienyl,benzofuryl, benzothienyl, pyridinyl or pyrimidinyl, each of which isoptionally mono- or di-substituted by identical or differentsubstituents, possible substituents being the abovementionedsubstituents on phenyl; or represents the groupings ##STR16## wherein R³represents fluorine or chlorine;

R⁴ represents hydrogen, fluorine or chlorine;

R⁵ represents vinyl, propargyl, the --CH═O group, methoximinomethyl,dimethoxymethyl or the dioxolane or 1,3-dioxane radical;

R⁶ represents cyano or phenyl which is optionally mono- ordi-substituted by identical or different substituents, possiblesubstituents being the substituents on phenyl which have already beenmentioned above, or represents the groupings --XR⁷ and --CONR⁸ R⁹ ;

wherein

R⁷ represents straight-chain or branched alkyl with 1 to 4 carbon atomsor halogenoalkyl with 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, such as fluorine and chlorine atoms, orrepresents phenyl or benzyl, each of which is optionally mono- ordi-substituted by identical or different substituents, possiblesubstituents in each case being the substituents on phenyl which havealready been mentioned above;

R⁸ represents hydrogen, methyl, ethyl, isopropyl or phenyl which isoptionally mono- or di-substitued substituted by identical or differentsubstituents, possible substituents being the substituents on phenylwhich have already been mentioned above;

R⁹ represents hydrogen, methyl or isopropyl;

X represents oxygen or sulphur and

n represents the number 0, 1 or 2.

The methyl ketones of the formula (II) are known or can be prepared in asimple manner by known processes.

Possible formylating agents both for carrying out the first stage ofvariant (a) and for carrying out the first stage of variant (b) are,formic acid alkyl esters with 1 to 4 carbon atoms in the alkyl group, orphenyl formate. These formylating agents are generally known compoundsof organic chemistry.

The formamidine to be used as a reaction component in carrying out the2nd stage of variant (a) or in carrying out the 3rd stage of variant (b)can be employed either as such or in the form of a salt with an organicor inorganic acid. Examples of acids which may be mentioned arehydrochloric acid and acetic acid.

Possible amino-formylating agents both for carrying out the 3rd stage ofvariant (a) and for carrying out the 2nd stage of variant (b) are allthe reagents which are customary for such purposes and which are capableof converting an activated methylene group into an enamine. Reagentswhich can preferably be used are:

(a) formamide acetals of the formula ##STR17## in which R¹² and R¹³independently of one another represent alkyl with 1 to 4 carbon atomsor, together with the nitrogen atom to which they are bonded, representan optionally substituted N-heterocyclic radical and

R¹⁴ represents alkyl with 1 to 4 carbon atoms,

(β) aminal esters of the formula

    R.sup.14 --O--CH(NR.sup.12 R.sup.13).sub.2                 (VIII)

in which

R¹², R¹³ and R¹⁴ have the abovementioned meaning;

and

(γ) formiminium halides of the formula ##STR18## in which R¹² and R¹³have the abovementioned meaning and Hal represents halogen.

In the abovementioned compounds of the formulae (VII), (VIII) and (IX),

R¹² and R¹³ independently of one another particularly preferablyrepresent methyl, ethyl, n-propyl, isopropyl or n-butyl, or

R¹² and R¹³, together with the nitrogen atom to which they are bonded,particularly preferably represent pyrrolidinyl, piperidinyl, morpholinylor N-methyl-piperazinyl.

In the compounds of the formulae (VII) and (VIII), R¹⁴ particularlypreferably represents methyl, ethyl or n-propyl.

In the compounds of the formula (IX), Hal particularly preferablyrepresents chlorine or bromine. The amino-formylating agents of theformulae (VII), (VIII) and (IX) are generally known compounds of organicchemistry.

In the compounds of the formulae (V) and (VI), the meaning of thesubstituent Y depends on which amino-formylating agent is used. Ifcompounds of the formulae (VII), (VIII) or (IX) are employed, compoundsof the formulae (V) or (VI) in which Y represents the grouping of theformula ##STR19## wherein R¹² and R¹³ have the abovementioned meanings,

are formed.

Preferred possible diluents for all the stages of both process variantsare inert, aprotic solvents. These include, preferably, ethers, such asdiethyl ether, diisopropyl ether, 1,2-dimethoxyethane andtetrahydrofuran; aromatic hydrocarbons, such as benzene, toluene andxylene; and aliphatic hydrocarbons, such as hexane and octane.

The formylation reaction according to the 1st stage of both processvariants is carried out in the presence of a strong base. All theorganic and inorganic bases which can usually be employed may be usedhere. Alkali metal alcoholates, such as sodium methylate, potassiumethylate, lithium propylate and potassium tert.-butylate, are preferablyused.

Possible acids which can be employed in carrying out the first stage ofprocess variants (a) and (b) for acidifying the reaction mixture are allthe acids customary for such purposes. Hydrochloric acid can preferablybe used.

The meaning of the substituent R¹⁰ in the compounds of the formula (III)varies depending on the base used in carrying out the first stage of theprocess according to the invention in variants (a) and (b) and dependingon whether the reaction mixture has been acidified in the first stage.If alkali metal alcoholates are used as the bases, compounds of theformula (III) in which R¹⁰ represents an alkali metal, such as, forexample, lithium, sodium or potassium, result. If the reaction mixtureis acidified, enol-ketones of the formula (III) in which R¹⁰ representshydrogen are formed.

The reaction temperature can be varied within a substantial range incarrying out the process according to the invention both in variant (a)and in variant (b). In general,

the 1st stage of both process variants is carried out between -25° and+60° C., preferably between -10° and +40° C.;

the 2nd stage of process variant (a) is carried out between -25° and+50° C., preferably between -10° and +10° C.;

the 3rd stage of process variant (a) and the 2nd stage of processvariant (b) are likewise carried out between -25° and +50° C.,preferably between -10° and +10° C.;

the reaction with formamidine according to the 3rd stage of processvariant (b) is carried out between -20° and +30° C., preferably between-10° and +10° C.; and

the cyclization by heat in the last stage of both process variants iscarried out between 0° and +100° C., preferably between +50° and +100°C.

In carrying out the process according to the invention, equimolaramounts or a slight excess, preferably up to 1.5 moles of formylatingagent, amino-formylating agent and formamidine are preferably employedper mole of methyl ketone of the formula (II) both in variant (a) and invariant (b). Working up and isolation of the compounds of the formula(I) and, if appropriate, also of the individual intermediates of theformulae (III), (IV), (V) and (VI) are carried out by customary methods.

As already mentioned, the 5-acylpyrimidines of the formula (I) areinteresting intermediates for the synthesis of substances with a plantgrowth-regulating and fungicidal activity. Thus, benzylpyrimidinyl-alkyl ethers of the formula ##STR20## in which Ar representsoptionally substituted phenyl and

R¹⁵ represents alkyl, optionally substituted cycloalkyl or optionallysubstituted phenyl,

are obtained by a process in which 5-acylpyrimidines of the formula##STR21## in which R¹⁵ has the abovementioned meaning,

are reduced in the customary manner and the pyrimidinylcarbinols thusobtained, of the formula ##STR22## in which R¹⁵ has the abovementionedmeaning, are reacted with benzyl halides of the formula

    Ar--CH.sub.2 --Hal                                         (XII)

in which

Ar has the abovementioned meaning and

Hal represents halogen,

in the presence of a solvent and, if appropriate, in the presence of astrong base (See U.S. Pat. No. 4,436,907 issued Mar. 13, 1984.)

The process according to the invention is illustrated by the followingexamples.

PREPARATION EXAMPLES Example 1 ##STR23## Process variant (a) withisolation of the intermediate of the formula (III-1) 1st stage

    (CH.sub.3).sub.3 C--CO--CH═CH--OK                      (III-1)

56.0 g (0.5 mole) of potassium tert.-butylate are added to a mixture of50.0 g (0.5 mole) of pinacolone and 42.0 g (0.5 mole) of methyl formateat 15° to 20° C., with cooling. The reaction mixture is subsequentlystirred at 30° C. for 12 hours. For working up, 400 ml of diethyl etherare added and the product precipitated is filtered off with suction anddried. 62.3 g (75% of theory) of 4,4-dimethyl-1-hydroxy-1-penten-3-one,as the potassium salt, are obtained in the form of a light yellowpowder.

2nd to 4th stage ##STR24##

132.1 g (1.27 moles) of formamidine acetate in 800 ml of tetrahydrofuranare added in portions to 166.2 g (1 mole) of the potassium salt of4,4-dimethyl-1-hydroxy-1-penten-3-one (compare 1st stage) in 800 ml oftetrahydrofuran at 0° C. The reaction mixture is subsequently stirred at0° C. for 15 minutes, and 165.4 g (1.39 moles) of N,N-dimethylformamidedimethyl acetal are then added. The mixture is subsequently stirred at0° C. for 1 hour and at 50° to 55° C. for 6 hours. For working up, it iscooled, the potassium acetate is filtered off with suction and thefiltrate is subjected to fractional distillation. 49.2 g (30% of theory)of tert.-butyl 5-pyrimidinyl ketone of boiling point bp₁₆ =102°-105° C.are obtained.

EXAMPLE 2 ##STR25## Process variant (a) wit isolation of theintermediate of the formula (III-2) 1st stage

    (CH.sub.3).sub.2 CH--CO--CH═CH--ONa                    (III-2)

344 g (4 moles) of isopropyl methyl ketone are first added dropwise to216 g (4 moles) of sodium methylate in 1.5 l of diethyl k ether at 25°C., and 296 g (4 moles) of ethyl formate are then added dropwise at30°-35° C. The reaction mixture is subsequently stirred at 25° C. forsix hours and the sodium salt precipitated is then filtered off withsuction. 360 g (66% of theory) of 1-hydroxy-4-methyl-1-penten-3-one, asthe sodium salt, are obtained.

2nd to 4th stage ##STR26##

240 g (2.308) moles of formamidine acetate in 1.5 l of tetrahydrofuranare added in portions to 250 g (1.84 moles) of the sodium salt of1-hydroxy-4-methyl-1-penten-3-one (compare 1st stage) in 1.5 l oftetrahydrofuran at 0° C. The reaction mixture is subsequently stirred at0° C. for 15 minutes, and 298 g (2.5 moles) of N,N-dimethylformamidedimethyl acetal are then added. The reaction mixture is subsequentlystirred at 0° C. for 1 hour and at 50°-55° C. for six hours. For workingup, the mixture is cooled and the sodium acetate is filtered off withsuction. The filtrate is subjected to fractional distillation. 91.6 g(33.2% of theory) of isopropyl 5-pyrimidinyl ketone of boiling pointbp₁₈ =112°-115° C. are obtained.

Example 3 ##STR27## Process variant (b) with isolation of theintermediate of the formula (III-3) 1st stage ##STR28##

300 g (1.94 moles) of 4-chloroacetophenone are added dropwise to asuspension of 105 g (1.94 moles) of sodium methylate in 1.7 l of diethylether. 144 g (1.94 moles) of ethyl formate are added dropwise at roomtemperature, with cooling. The reaction mixture is stirred under refluxfor 3 hours and cooled to room temperature and the precipitate isfiltered off with suction. The precipitate is dissolved in water, the pHvalue is brought to 1-2 with dilute hydrochloric acid, the mixture isextracted with ethyl acetate and the organic phase is concentrated. 216g (61% of theory) of 4-chlorophenyl hydroxyvinyl ketone of melting point44° C. are obtained.

2nd and 3rd stage ##STR29##

7.7 g (0.065 mole) of N,N-dimethylformamide dimethyl acetal are added inportions to 10 g (0.055 mole) of 4-chlorophenyl hydroxyvinyl ketone(compare 1st stage) in 10 ml of toluene at 0° C. The reaction mixture issubsequently stirred for 15 minutes, and 5.7 g (0.055 mole) offormamidine kacetate are then added. After further subsequent stirringfor 15 minutes, a solution of 3 g (0.055 mole) of sodium methylate in 80ml of ethanol is added dropwise and the mixture is subsequently stirredunder reflux for 8 hours. The reaction mixture is allowed to cool and ispoured onto 400 ml of water and extracted with toluene. The organicphase is washed with water, dried over sodium sulphate and concentrated.The residue is purified by column chromatography (ethyl acetate:cyclohexane=3:1; silica gel). 3.7 g (31% of theory) of 4-chlorophenyl5-pyrimidinyl ketone of melting point 110°-112° C. are obtained.

The following 5-acylpyrimidines of the formula (I) ##STR30## can beobtained analogously and in accordance with the process conditionsdescribed:

    ______________________________________                                        Ex-                                                                           am-                                                                           ple                                                                           No.  R                   Physical constants                                   ______________________________________                                              ##STR31##          Melting point: 106° C.                        5                                                                                   ##STR32##          n.sub.D.sup.20 = 1.5473                              6                                                                                   ##STR33##          Melting point: 178° C.                        7                                                                                   ##STR34##          Melting point: 58° C.                         8    CH.sub.3 OCH.sub.2C(CH.sub.3).sub.2                                                               n.sub.D.sup.20 = 1.4964                              9                                                                                   ##STR35##          Melting point: 62° C.                         10                                                                                  ##STR36##          Melting point: 64° C.                         11                                                                                  ##STR37##          Melting point: 95° C.                         12                                                                                  ##STR38##          Melting point: 90-92° C.                      ______________________________________                                    

Preparation of benzyl pyrimidinyl-alkyl ethers of the formula (X)Example (X-1) ##STR39## Preparation of the starting substance ##STR40##

1.27 g (0.034 mole) of sodium borohydride in 10 ml of water are added to16.4 g (0.1 mole) of tert.-butyl 5-pyrimidinyl ketone in 100 ml ofmethanol at room temperature. The reaction mixture is stirred at roomtemperature for 1 hour and concentrated in vacuo, the residue isdistilled in methylene chloride and the solution is concentrated againin vacuo. 15.8 g (95% of theory) of5-(1-hydroxy-2,2-dimethyl-propyl)-pyrimidine of melting point 93°-95° C.are obtained.

Preparation of the end product ##STR41##

200 ml of 33% strength aqueous sodium hydroxide solution are added to asolution of 16.6 g of 5-(1-hydroxy-2,2-dimethyl-propyl)-pyrrimidine,32.2 g of 4-chlorobenzyl chloride and 6 g of te trabutylammonium bromidein 200 ml of toluene. The reaction mixture is stirred vigorously at roomtemperature for 18 hours.

The aqueous phase is separated off and the organic phase is diluted withtoluene, washed four times with water and once with saturated aqueoussodium chloride solution, dried over sodium sulphate and concentrated.The oily residue is dissolved in ether/hexane and the solution is gassedwith hydrogen chloride. The crystalline precipitate formed is filteredoff with suction and rinsed with ether, and ethyl acetate/1N aqueoussodium hydroxide solution is added whereupon the free base is formedagain.

After recrystallization from hexane, 20.3 g (70% of theory) of5-[1-(4-chlorobenzyloxy)-2,2-dimethylpropyl]-pyrimidime of melting point77°-78.5° C. are obtained.

Example (X-2) ##STR42## Preparation of the starting substance ##STR43##

1.27 g (0.034 mole) of sodium borohydride in 10 ml of water are added to15 g (0.1 mole) of isopropyl 5-pyrimidinyl ketone in 100 ml of methanolat room temperature. The reaction mixture is subsequently stirred atroom temperature for 1 hour and is concentrated in vacuo, the residue istaken up in methylene chloride and the mixture is concentrated again invacuo. 15.1 g (99.3% of theory) of5-(1-hydroxy-2-methyl-propyl)-pyrimidine of refractive index n_(D) ²⁰=1.5082 are obtained.

Preparation of the end product ##STR44##

100 ml of 33% strength aqueous sodium hydroxide solution are added to asolution of 6.8 g of 5-(1-hydroxy-2-methyl-propyl)-pyrimidine, 14.5 g of4-chlorobenzyl chloride and 3 g of tetrabutylammonium bromide in 100 mlof toluene. The reaction mixture is stirred at room temperature for 2days.

The aqueous phase is separated off and the organic phase is diluted withtoluene, washed four times with water and once with saturated aqueoussodium chloride solution, dried over sodium sulphate and concetrated.The oily residue is dissolved in ether/hexane and the solution is gassedwith hydrogen chloride. The crystalline precipitate formed is filteredoff with suction and rinsed with ether, and ethyl acetate/1N aqueoussodium hydroxide solution is added, whereupon the free base is formedagain.

10.2 g (82% of theory) of5-[1-(4-chloro-benzyl-oxy)-2-methylpropyl]-pyrimidine are obtained as alight oil which slowly crystallizes completely (melting point 33°-35°C.).

Comparison Example Preparation of5-(1-hydroxy-2,2-dimethyl-propyl)-pyrimidine of the formula (XI-1) bythe process known hitherto ##STR45##

225 g of 5-bromopyrimidine are dissolved in 1.5 l of absolutetetrahydrofuran/1,000 ml of absolute ether and the solution is cooled to-120° C. 250 ml of 50% strength n-butyl-lithium (in n-hexane) are addeddropwise at an internal temperature of -105° to -115° C. in the courseof 2 hours. The mixture is subsequently stirred at this temperature for1 hour. 309 ml of trimethylacetaldehyde are then added dropwise in thecourse of 2 hours. The reaction mixture is then subsequently stirred atthis temperature for 4 hours. It is allowed to warm to room temperatureovernight and 83 g of ammonium chloride, dissolved in a minimum amountof water, are then added. The aqueous phase is separated off and theorganic phase is washed twice with saturated sodium chloride solution,dried over sodium sulphate and concentrated. After recrystallization ofthe residue from acetonitrile, 155 g (66% of theory) of5-(1-hydroxy-2,2-dimethylpropyl)pyrimidine of melting point 94°-96° C.are obtained.

It is understood that the specification and examples are illustrativebut not limitative of the present invention and that other embodimentswithin the spirit and scope of the invention will suggest themselves tothose skilled in the art.

We claim:
 1. A 5-acyl-pyrimidine of the formula ##STR46## in which R¹¹represents phenyl which is mono-or di-substituted by fluorine, chlorine,methyl, ethyl, isopropyl, tert.-butyl, methoxy, methylthio,trifluoromethyl, trifluoromethoxy and/or trifluoromethylthio; orrepresents the grouping ##STR47## in which R⁶ represents phenyl which isoptionally mono-or di-substituted by fluorine, chlorine and/or bromine;or represents the grouping --XR⁷ ;R⁷ represents alkyl with 1 to 4 carbonatoms or phenyl which is optionally mono- or di-substituted by chlorine;X represents oxygen or sulphur, and n represents the number 0 or 1.